According to research published in Blood, patients with hereditary thrombotic thrombocytopenic purpura (hTTP) have life-altering neuropsychiatric symptoms that begin at young ages and continue throughout their lives.

Researchers evaluated the long-term neurological effects in patients with hTTP by documenting their rates of stroke, stroke-related disability, and presence of neuropsychiatric symptoms.

The researchers conducted telephone interviews with patients or parents of minors with genetically or biochemically confirmed hTTP living in the United States who had enrolled in the International hTTP Registry.

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The interview was based on discussion guides tailored to young children (≤6 years old), older children (7-17 years), or adults (≥18 years old). The interviewer asked participants about neuropsychiatric symptoms and stroke, the age at which they occurred, hospitalizations, and residual symptoms or disability as well as prophylaxis, when it began, and any adverse reactions.

A total of 27 patients (female, 70%; male, 30%) were interviewed between April 2020 and July 2021. Among those, there were 25 adults (median age, 38 years; range, 19-63) and 2 children (age, 20 months and 12 years). The participants were predominantly White (89%).

For 14 neuropsychiatric symptoms, 96% of patients reported 2 to 14 (median, 6) symptoms, with symptom onset occurring across all ages. Commonly reported symptoms included recurrent headaches (88%), poor concentration (65%), and depression (62%). Some patients (15%) also reported headache with aura (presumed migraine).

Of the queried symptoms, dysarthria was the only symptom more common in patients with a history of stroke than those with no history of stroke (56% vs 10%; P =.04). Patients often described their symptoms as beginning during “childhood,” during “high school,” or after a significant hTTP event, suggesting that patients of all ages are at risk of neuropsychiatric symptoms.

Stroke was reported by 63% of patients, with the median age of first stroke at 26 years (range, newborn-58 years). The researchers found that the occurrence of stroke increased with age, with 100% of patients ≥49 years of age having had a stroke. They also found that stroke often preceded diagnosis of hTTP (44%) and that 65% of patients who experienced ≥1 stroke had residual symptoms. Recurrent strokes were reported by 7 patients (41%) and stroke-related disability benefits were being received by 7 patients (41%), beginning at a median age of 43 years (range, 18-55 years).

Most (93%) patients reported receiving plasma for treatment of symptoms or as prophylaxis. Allergic reactions to plasma were reported by 21 patients; these included rash/itching (n=14), dyspnea/chest pain (n=4), anaphylaxis (n=2), or hepatitis C infection (n=1).

At the time of interview, 63% patients were on prophylaxis (plasma, 12; plasma-derived FVIII, 5), which was initiated at a median of 30 years of age (range, 2 months-63 years) and continued for a median duration of 4.5 years (range, 1-53).

“Our data document that almost all patients have neuropsychiatric symptoms, suggesting the need for regular cognitive and depression screening of hTTP and effective prophylaxis when abnormalities are identified,” the researchers concluded in their report.

Because strokes often preceded the diagnosis of hTTP, the researchers emphasized the importance of ADAMTS13 activity measurement in patients with an embolic stroke of undetermined source. They also stressed the importance of beginning effective, lifetime prophylaxis at a young age instead of the current common practice of initiating it after a major complication has occurred. They recommended that baseline cerebral magnetic resonance imaging be conducted at the first occurrence of neuropsychiatric symptoms to identify silent strokes and document the need for prophylactic therapy.

Limitations of the study included the small number of patients due to the rarity of the disorder and potential for selection bias, as enrollment in the International hTTP Registry may be limited by lack of patient or hematologist motivation or awareness.

Disclosure: This research was supported by Takeda, Inc. Please see the original reference for a full list of disclosures.


Borogovac A, Tarasco E, Kremer Hovinga JA, et al. Prevalence of neuropsychiatric symptoms and stroke in patients with hereditary thrombotic thrombocytopenic purpura. Blood. 2022;140(7):785-789. doi:10.1182/blood.2022016044